Cell-specific regulation of neuronal production in the larval frog retina

Abstract

We have previously postulated the existence of a feedback mechanism from differentiated neurons that regulates the production of new neurons. Evidence for such regulatory feedback comes from experiments in which dopamine-containing amacrine cells, ablated in the developing retina by 6-hydroxydopamine (6-OHDA), were up-regulated in their production. To determine whether this is a general phenomenon of the developing retina, the neurotoxin kainic acid (KA) was injected intraocularly in midlarval-stage Rana pipiens tadpoles to produce selective lesions of certain retinal cell types. After periods of 1-21 d, the animals received intraperitoneal injections of 3H-thymidine. Animals were then allowed to survive for periods of up to 3 weeks and were then fixed, the eyes embedded in plastic, sectioned at 3 micron, and processed for autoradiography by standard methods. At the dosage used, the KA produced a 52% decline in the cell density of the inner nuclear layer (INL), a 37% decline in the retinal ganglion cell layer (RGC), and no significant change in the density of cells in the outer nuclear layer (ONL). The 3H-thymidine allowed us to detect any changes in the number of new cells added to the retina after the KA lesion. Within the first week after the KA injection, there was a decrease in the number of 3H-thymidine (3H-Thy)-labeled cells in the lesioned eye as compared to in the control retina; however, KA treatment of slice cultures demonstrated that the toxin does not affect proliferating neuroblasts directly.(ABSTRACT TRUNCATED AT 250 WORDS)